ETV6 and ETV7: Siblings in hematopoiesis and its disruption in disease

- ETV6 and ETV7 are closely related, with both similar and antagonistic functions.
- ETV6 and ETV7 regulate different aspects of hematopoiesis, with ETV6 a tumor suppressor and ETV7 an oncogene.
- Analysis of ETV6 mutation status is recommended for a range of hematological malignancies to inform prognosis and treatment.
- Germline ETV6 mutation analysis is warranted in families with ALL and/or thrombocytopenia, along with on-going surveillance.

ETV6 (TEL1) and ETV7 (TEL2) are closely-related members of the ETS family of transcriptional regulators. Both ETV6 and ETV7 have been demonstrated to play key roles in hematopoiesis, particularly with regard to maintenance of hematopoietic stem cells and control of lineage-specific differentiation, with evidence of functional interactions between both proteins. ETV6 has been strongly implicated in the molecular etiology of a number of hematopoietic diseases, including as a tumor suppressor, an oncogenic fusion partner, and an important regulator of thrombopoiesis, but recent evidence has also identified ETV7 as a potential oncogene in certain malignancies. This review provides an overview of ETV6 and ETV7 and their contribution to both normal and disrupted hematopoiesis. It also highlights the key clinical implications of the growing knowledge base regarding ETV6 abnormalities with respect to prognosis and treatment.